GI bleedingGI bleeding

A Aljebreen, MD, FRCPCA Aljebreen, MD, FRCPC

BackgroundBackground UGIB has a prevalence of ~ 170 cases per 100 000

adults per year (US data) In Southern SA, 31 per 100,000 population > age of 20.

The commonest causes were oesophageal varices (30%), gastritis and erosions (25%) and duodenal ulcers (22%)

Despite recent advances in therapy, mortality rates have remained essentially unchanged for the past half century at 6-8% Pts are older and consequently more co-morbidities ? Under use of endoscopic hemostatic techniques.

Silverstein et al, GI Endosc. 1981;27:80-93.Barkun et al. Am J Gastroenterol. 2001;96:S261.

Etiology of non-variceal UGIBEtiology of non-variceal UGIB

PUD

errosions

MWT

others

Huang et al, Gastroenterol Clin N Am 32 (2003)

Case presentationCase presentation

75 Y.O F known to have IHD, DM, HTN on 75 Y.O F known to have IHD, DM, HTN on ASA presented with 3 days h/o melena ASA presented with 3 days h/o melena and dizziness.and dizziness.

On ER, drowsy, very pale, SBP 50, On ER, drowsy, very pale, SBP 50, HR=100.HR=100.

Hg= 5.3.Hg= 5.3.

CaseCase

Initial management?Initial management?What is the role of resuscitation?What is the role of resuscitation? Is there any role for NG aspirate?Is there any role for NG aspirate?Risk stratification?Risk stratification?Role for urgent endoscopyRole for urgent endoscopyRole for pharmacotherapyRole for pharmacotherapy

Risk stratificationRisk stratification

Approximately 80% of patients will stop bleeding spontaneously without recurrence.

Most morbidity and mortality occur among the remaining 20%.

Thus, the main goal of management is to identify patients at high risk for an adverse outcome on the basis of clinical, laboratory and endoscopic variables

Clinical predictors of re-bleedingRisk factorRisk factor Odds RatioOdds Ratio

Age>65 y>70 y

1.31.3

2.32.3

Shock 1.2-3.651.2-3.65

Health status ASA class 1 1.94-7.361.94-7.36

Comorbid illness 1.6-7.631.6-7.63

Erratic mental status 3.103.10

Ongoing bleeding 3.143.14

Melena 1.61.6

Red blood on PR 3.763.76

Red blood on NG 1.11-11.61.11-11.6

Hematemesis 1.2-5.71.2-5.7

Coagulopathy 1.961.96

Barkun et al, Ann Int Med Nov 2003

Endoscopic predictors of rebleeding

Risk factor Odds Ratio

Active bleeding on endoscopy 2.5-6.5

Endoscopic HR stigmata 1.9-4.8

Clot 1.8

Ulcer >2cm 2.3-3.5

Diagnosis of GU or DU 2.7

Ulcer locationHigh on lesser curvatureSuperior wallPosterior wall

2.813.99.2

Barkun et al, Ann Int Med Nov 2003

Predictors of deathRisk Factor Odds Ratio

Age >60 3.5-5.7

Shock 1.2-5.2

ASA classification 2.6-9.5

Comorbidity 1.2-12.1

Persistent bleeding 5.3-76

Red NG aspirate 0.4-18

Hematemesis 2

Red blood on PR 3

Bleeding while on hospital 2.8

Elevated BUN 5.5-18

Creatinine >150 15

Elevated AST 4-20

Sepsis 5.4

Barkun et al, Ann Int Med Nov 2003

NG role in UGIB: Conclusion

The presence of blood in naso-gastric aspirate confirms an upper GI source.

The detection of red blood with an in-and-out NG tube has been shown to predict poor outcome.

NGA is useful in predicting HRL. NGA is useful in predicting HRL. It may help to determine which patients It may help to determine which patients

would benefit from earlier endoscopy.would benefit from earlier endoscopy.Aljebreen et al, GI endoscopy Feb 2004 Perng et al, Am J Gastroenterol. 1994;89:1811-4.

Prognostic scales Blatchford Score (non-endoscopic, <4 vs >5):

patients’ admission hemoglobin level, blood urea level, pulse, systolic blood pressure, presence of syncope or melena, and evidence of hepatic disease or cardiac failure.

Rockall risk score, has a max score of 11 and includes age, presence of shock, comorbid conditions, diagnosis, and endoscopic stigmata of recent hemorrhage

Blatchford et al, Lancet. 2000;356:1318-21Rockall et al, Lancet. 1996; 347:1138-40

Endoscopic Therapy: ?urgent Endoscopic Therapy: ?urgent EndoscopyEndoscopy

Indications of urgent Gastroscopy:Indications of urgent Gastroscopy: If pt presented with hemodynamic instability If pt presented with hemodynamic instability

(tachycardic and or hypotension)(tachycardic and or hypotension) If pt presented with few hrs h/o significant If pt presented with few hrs h/o significant

hematemesishematemesis If had Red NG aspirateIf had Red NG aspirate

Endoscopic Therapy

The three chief methods of endoscopic The three chief methods of endoscopic therapy aretherapy are: : ((11) ) thermal contact methods thermal contact methods ((heater probe, heater probe,

multipolar electrocoagulationmultipolar electrocoagulation)), , ((22) ) injection with dilute epinephrineinjection with dilute epinephrine.. (3) Hemoclips(3) Hemoclips

Endoscopic Therapy: recommendations

Low-risk endoscopic stigmata (a clean-based ulcer or a nonprotuberant pigmented dot in an ulcer bed) No need for endoscopic hemostatic therapy

A clot in an ulcer bed warrants targeted irrigation in an attempt at

dislodgment, with appropriate treatment of the underlying lesion

High-risk endoscopic stigmata (active bleeding or a visible vessel in an ulcer bed) is an indication for immediate endoscopic hemostatic

therapySacks et al, JAMA. 1990;264:494-9.Cook et al, Gastroenterology. 1992;102:139-48.

Adherent ClotAdherent Clot

The optimal management of adherent clots has long been controversial.

The risk for rebleeding with clots reported as only 8% in 1 study but as high as 25-29% in others.

Two recent studies found that endoscopic therapy for adherent clots statistically significantly reduced the rate of re-bleeding compared with medical therapy alone

Bleau et al, GI Endosc. 2002;56:1-6.Jensen et al, Gastroenterology. 2002;123: 407-13.

Injection vs thermo or electro-coagulationInjection vs thermo or electro-coagulation??

Most individual randomized studies have shown no differences in rates of re-bleeding, surgery, and mortality among coaptive therapy with heater probe thermocoagulation, multipolar electro-coagulation,

when compared with injection therapy

Chung et al, Gastroenterology. 1991;100:33-7.Lin et al, Gut. 1990;31:753-7.

APCAPC??

in 185 patients with high-risk lesions, a randomized study, suggested no difference between injection plus heater probe and injection plus argon plasma coagulation

Chau et al, Gastrointest Endosc. 2003;57:455-61.

Monotherapy vs combination therapyMonotherapy vs combination therapy

Combination treatment was associated with statistically significant reductions in absolute rates of rebleeding compared with injection

alone, thermal treatment alone, or pharmacotherapy.

Similar reductions in rebleeding were not observed when the combination was compared with hemoclip therapy alone, despite statistically significant reductions in surgery rates.

Bardou M, Barkun A. [Abstract]. Gastroenterology. 2003;123:A239.Jensen et al, Gastroenterology. 2002;123: 407-13.Lin et al, Gut. 1999;44:715-9.

The placement of clips

Endoscopic clips have shown superiority over heater probe or injection therapy in 2 trials but higher failure rates compared with injection therapy in another.

Studies of the combination of injection plus endoscopic clips have demonstrated no statistically significant benefit over injection alone or clips alone.

Cipolletta et al. Endoclips versus heater probe GI Endosc. 2001; 53:147-51.Gevers et al, Gastrointest Endosc. 2002;55:466-9.157

Re-bleeding: Endoscopic Re-Re-bleeding: Endoscopic Re-treatment Vs Surgerytreatment Vs Surgery

In the only randomized comparison, immediate endoscopic retreatment in patients with rebleeding after endoscopic hemostasis reduced the need for surgery without increasing the risk

for death and was associated with Fewer complications than surgery (143).

Lau et al. N Engl J Med. 1999;340:751-6.

Pharmacotherapy: H2-RA vs PPI A recent meta-analysis by Levine and coworkers

concluded that intravenous H2-RA provided no additional benefit in bleeding duodenal ulcers but provided small but statistically significant absolute risk reductions in rebleeding (7.2%), surgery (6.7%), and death (3.2%) in patients with bleeding gastric ulcer compared with placebo.

Recent meta-analyses have found PPI to be more effective than H2-RA or placebo in preventing persistent or recurrent bleeding and surgery in selected patients.

Selby et al, Aliment Pharmacol Ther. 2000;14:1119-26. Levine et al, Aliment Pharmacol Ther. 2002;16:1137-42.Zed et al, Ann Pharmacother. 2001;35:1528-34.

IV PPIIV PPI An IV bolus followed by continuous-infusion PPI

is effective in decreasing re-bleeding in patients who have undergone successful endoscopic therapy. 80-mg bolus followed by 8 mg/h for 72 hours after

endoscopic therapy. Four RCTs assessing high-dose bolus and

continuous-infusion PPI (high-risk stigmata following endoscopic therapy), have shown decreased rebleeding and, in some cases, reduced need for surgery compared with H2-RA or

placebo.

Lau et al, N Engl J Med. 2000;343:310-6.

Empirical PPIEmpirical PPI?? Two studies in Asia compared oral omeprazole, 40 mg

every 12 hours for 5 days, with either placebo (without endoscopic therapy) or endoscopic injection of alcohol for high-risk lesions.

A third study compared the same omeprazole dosage after endoscopic injection therapy with placebo (172).

All showed decreased re-bleeding with or without decreased rates of surgery.

A study from Iran using oral omeprazole, 20 mg every 6 hours for 5 days also suggested decreased re-bleeding compared with placebo after injection hemostasis.

Khuroo et al, N Engl J Med. 1997;336:1054-8. Jung et al, Am J Gastroenterol. 2002;97:1736-40. Javid et al, Am J Med. 2001;111:280-4.Kaviani et al, Aliment Pharmacol Ther. 2003;17:211-6.

H. Pylori Eradication Eradication of H. pylori has been demonstrated, in a

meta-analysis of selected patients with duodenal ulcers not associated with NSAIDs intake and in many randomized, controlled trials, to reduce: the rate of ulcer recurrence and Re-bleeding in complicated ulcer disease.

Most tests of active infection may exhibit increased false-negative rates in the context of acute bleeding.

The diagnostic approach may include acute testing for H. pylori infection, followed, if results are negative, by a confirmatory test outside the acute context of bleeding.

Sharma et al, Aliment Pharmacol Ther. 2001;15:1939-47.Graham et al, Scand J Gastroenterol. 1993;28:939-42.Rokkas et al, Gastrointest Endosc. 1995;41:1-4.

UGIB

Hemodynamic stabilization

NG aspirate

Red and/or high risk clinical factors

Urgent endoscopy Elective endoscopy

Clear NG and no clinical risk factors

Low risk endoscopic stigmata HR stigmata

Low risk endoscopic

stigmata

Early feeding and discharge

Endoscopic therapy

Admit to ICU

Low clinical RF

Early feeding and discharge

High clinical RF

Observe in hospital for 48-72 hrs

Esophageal VaricesEsophageal Varices

DefinitionDefinition

Main complication of cirrhosis , common Main complication of cirrhosis , common and lethal: varices and ascitesand lethal: varices and ascites

Threshold:Threshold:10 to 12 mm Hg10 to 12 mm Hg

Natural HistoryNatural History

varices present in 50% with cirrhosisvarices present in 50% with cirrhosisassociated with severity of liver disease associated with severity of liver disease risk of bleed 10% - 30% / yr.risk of bleed 10% - 30% / yr.

12 mm Hg threshold12 mm Hg thresholdwall tensionwall tension

Mortality 50%Mortality 50%20% rebleed20% rebleed

TherapyTherapy

PharmacologyPharmacology intrahepatic resistanceintrahepatic resistancePV flow splanchnic vasoconstrictorsPV flow splanchnic vasoconstrictorsblood volume blood volume

-blockers: po longterm-blockers: po longtermVasopressins: IV - acute Vasopressins: IV - acute

- adrenergic blockers- adrenergic blockers

1) 1) C.O. (B C.O. (B11))

2) splanchnic vasoconstriction (B2) splanchnic vasoconstriction (B2 2 + +

unopposed unopposed 1 1 ))

Vasopressin (terlipressin)Vasopressin (terlipressin)

splanchnic vasoconstrictionsplanchnic vasoconstrictionside effects: HBP, ischemiaside effects: HBP, ischemia

Portosystemic ShuntsPortosystemic Shunts(Surgery vs TIPS)(Surgery vs TIPS)

Communication between hypertensive Communication between hypertensive portal system and low pressure systemic portal system and low pressure systemic circulationcirculation

Cx: shunt away from liver - HE, ALFCx: shunt away from liver - HE, ALF

Endoscopic Treatment Endoscopic Treatment (sclero vs EVL)(sclero vs EVL)

local, non pressure reducing methodlocal, non pressure reducing method temporarytemporarycomplications (sclero > EVL)complications (sclero > EVL)

Recommendations - 1st bleed- Recommendations - 1st bleed- screeningscreening

1) non selective 1) non selective -blocker: therapy of -blocker: therapy of choice if large varices, lower HR by 25% choice if large varices, lower HR by 25% resting or 55 to 60/min. (HPVG by 20% or resting or 55 to 60/min. (HPVG by 20% or < 12 mm Hg).< 12 mm Hg).

2) EVL if not tolerated by 2) EVL if not tolerated by -blockers-blockers3) if small varices, rescope Q1 -2 years3) if small varices, rescope Q1 -2 years

Acute Variceal HemorrhageAcute Variceal Hemorrhage

General MeasuresGeneral MeasuresAB prophylaxis (norflox 400 mg BID x 7 days)AB prophylaxis (norflox 400 mg BID x 7 days)cautious blood transfusioncautious blood transfusion

Pharmacology:Pharmacology: ideal when drugs safe and effective ideal when drugs safe and effective can misdiagnose for early treatmentcan misdiagnose for early treatmentSMS, terlipressinSMS, terlipressinwill control 80% will control 80%

octreotide? As good as SMS octreotide? As good as SMS

Endoscopic treatmentEndoscopic treatmentsclero-: controls approx. 90%sclero-: controls approx. 90%EV: less sessions, less rebleed, less CxEV: less sessions, less rebleed, less Cx

combo (endoscopic and meds)combo (endoscopic and meds) interesting interesting SMS x 5 days > endo: sclero aloneSMS x 5 days > endo: sclero alone? EVL? EVL? Octreotide? Octreotide10 - 20 % continue to bleed or rebleed10 - 20 % continue to bleed or rebleedsurg. Shunt. (CP Class A) or TIPS as surg. Shunt. (CP Class A) or TIPS as

salvagesalvage

RecommendationRecommendation

1) endoscopic Tx (EVL > sclero)1) endoscopic Tx (EVL > sclero)2) adjust SMS probably better2) adjust SMS probably better3) shunt as salvage therapy3) shunt as salvage therapy4) balloon tamponade effective but 4) balloon tamponade effective but

temporarytemporary+++ Cx+++ Cxon the way to shunting on the way to shunting

Prevention of recurrent bleedPrevention of recurrent bleed

Sclero = Sclero = -blocker ( 60% -blocker ( 60% 40%) 40%)more side effects with scleromore side effects with sclero

-blocker = ISMN > sclero = -blocker = ISMN > sclero = -blocker-blockerone study less survivalone study less survival

EVL is the standardEVL is the standardEVL + EVL + -blocker 47% vs EVL 23%-blocker 47% vs EVL 23%TIPS less rebleed but HE, TIPS less rebleed but HE,

occlusion/stenosisocclusion/stenosis

RecommendationRecommendation

1) 1) -blocker or EVL (expertise, tolerance, -blocker or EVL (expertise, tolerance, compliance )compliance )

2) combo if fail, one or the other2) combo if fail, one or the other3) if fail combo 3) if fail combo shunt shunt